The main aim of this project is to study the role of the autonomic nervous system in the regulation of energy metabolism and its possible contribution to the pathophysiology of obesity and type 2 diabetes. We use microneurography to measure muscle sympathetic nerve activity (MSNA) and plasma/urine catecholamines to measure global sympathetic nervous system (SNS) activity. We use fasting and post-prandial pancreatic polypeptide, pupillometry, heart rate/blood pressure tests, and gastric emptying rate to assess parasympathetic nervous system (PNS) activity. In the past year we have: a)established that suppression of cortisol does not improve the reduced MSNA in Pimas b)initiated a collaborative study to assess possible differences in 11-beta-HSD activity, a tissue specific modulator of cortisol sensitivity, in Pimas and Caucasians; c)continued a study on the role of PNS in insulin secretory function in Pimas and Caucasians; d)initiated a study on the SNS response to a standard meal in Pimas and Caucasians